ACTIVATION OF SEROTONIN(1A) RECEPTORS INHIBITS MIDBRAIN PERIAQUEDUCTAL GRAY NEURONS OF THE RAT

The midbrain periaqueductal gray (PAG) is involved in a variety of functions including pain modulation, vocalization, autonomic control, fear and anxiety. This area contains serotonin receptors, particularly 5-HT1A that are known to play a role in the above functions. The goals of this study were to characterize the effects of 8-OH-DPAT, a selective 5-HT1A agonist, on the firing characteristics and membrane properties of PAG neurons. Both in vivo and in vitro preparations were used. The effects of 8-OH-DPAT on baseline activity of 91 neurons were tested in the in vivo preparation. In 50/91 cells, 8-OH-DPAT produced a decrease in the firing rate that ranged between 21 and 98% (mean +/- S.E.M. decrease of 49 +/- 1.9%). This inhibitory effect was dose dependent and could be blocked by spiperone. In 10/91 cells, 8-OH-DPAT produced an increase in the firing rate that ranged between 13 and 290%, with mean increase of 83 +/- 7.4%. The baseline firing rate of the remaining 31 cells was not affected by 8-OH-DPAT. In the PAG slice preparation, the effects of 8-OH-DPAT on synaptic and membrane properties of 17 PAG neurons were tested using whole-cell voltage clamp-recording procedures. In 14 cells, application of 8-OH-DPAT produced hyperpolarization that ranged between 6 and 21 mV, with mean of 8.4 +/- 2.0 mV. This hyperpolarization was associated with a decrease in membrane impedance that ranged between 8 and 45%, with mean decrease of 21.6 +/- 4.5%. The remaining three neurons did not respond to 8-OH-DPAT. Under voltage clamp conditions and in the presence of TTX, application of 8-OH-DPAT produced a reversal potential that ranged between -70 and -90 mV, with mean of -80 +/- 2.68 mV. In conclusion: (1) 8-OH-DPAT has a strong influence on neurons in all regions of the PAG in particular on cells located in the dorsal PAG; (2) in both in vivo and in vitro preparations, the 5-HT1A-mediated response of PAG neurons is inhibitory; and (3) the inhibitory effect of 5-HT1A is associated with hyperpolarization of the cell membrane that is likely due to an increase in K conductance.